Abstract 5092: Predictive biomarkers for the efficacy of PD-1 inhibitors plus chemotherapy for gastric/gastroesophageal junction cancer in first-line setting
Authors: Yu-Ting Sun, Shi-Xun Lu, Ming-Yu Lai, Xia Yang, Wen-Long Guan, Li-Qiong Yang, Yu-Hong Li, Feng-Hua Wang, Rui-Hua Xu, Miao-Zhen Qiu
Journal: Cancer Research (2022)

Abstract Background: Biomarkers that could predict the beneficial effects of immune checkpoint inhibitors (ICIs) in combination with chemotherapy in treatment-naive advanced or recurrent gastric or gastroesophageal junction ﻿(G/GEJ) adenocarcinoma patients are lacking. Methods: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with programmed death-1 (PD-1) inhibitor plus chemotherapy between October 2017 and July 2021. Comparative analysis of the objective response rate (ORR) was performed using the Chi-square or Fisher’s exact tests. Survival curves were plotted by the Kaplan-Meier analysis and compared for significance with a log-rank test. Univariate and multivariate Cox proportional hazard models were established for evaluating the prognostic value of clinicopathological factors. Results: Of the 172 enrolled patients, 142 showed measurable lesions. The ORR was 52.8%. Higher response rates were observed in patients with age greater than or equal to 60 (p = 0.013), non-diffuse type (p &amp;lt; 0.001), synchronous metastasis (p = 0.029), distant lymph node metastasis (p = 0.002), non-peritoneal metastasis (p= 0.002), HER2 positivity (p = 0.002), and PD-L1 CPS greater than or equal to 5 (p = 0.017). Through univariate analysis, age, histology, number of metastatic sites, and peritoneal metastasis were found to be associated with progression-free survival (PFS). Through multivariate analysis, peritoneal metastasis occurrence was the only identified independent indicator of poor PFS (HR 2.768, 95% CI 1.184-6.472, p = 0.019). Additionally, multi-factor combination results showed that patients with at least one of the following: mismatch repair-deficient (D-MMR)/microsatellite instability-high (MSI-H), HER2 (+), EBV (+), and/or PD-L1 CPS greater than or equal to 5, exhibited higher response rates and longer PFS as compared to those lacking these factors; this benefit was consistent after excluding PD-L1 expression. Among the clinical combinatorial factors, significantly poor ORRs and lower PFS were observed in patients with age &amp;lt; 60, diffuse type, and peritoneal metastasis as compared to those without any of these factors.﻿ Conclusions: Peritoneal metastasis was an independent biomarker of poor efficacy to immunotherapy combined with chemotherapy in G/GEJ cancer patients in first-line setting. Some combination factors could be beneficial for efficacy prediction. Citation Format: Yu-Ting Sun, Shi-Xun Lu, Ming-Yu Lai, Xia Yang, Wen-Long Guan, Li-Qiong Yang, Yu-Hong Li, Feng-Hua Wang, Rui-Hua Xu, Miao-Zhen Qiu. Predictive biomarkers for the efficacy of PD-1 inhibitors plus chemotherapy for gastric/gastroesophageal junction cancer in first-line setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5092.